The broad aim of the project is to investigate a portion of the behavioral pharmacology (effects on ingestion) of one class of cannabinoid compounds. These drugs, which are categorized as antagonists (although pharmacologically they are inverse agonists), essentially block activity at the cannabinoid receptors located in the central nervous system (CB1 receptors). One of the recently demonstrated effects of CB1 receptor stimulation is an increase in intake of a variety of foods and conversely some evidence exists that blocking these receptors results in decreases in food intake. This pattern of effects following receptor activation and blockade mimics those for other classes of compounds which have been shown to affect ingestion, such as opioids and various serotonergic agents. Some of these latter compounds have been used in clinical attempts to mediate appetite and the long-term goal of the present research is to increase knowledge and potential application of cannabinoid antagonists as appetite control drugs. The need for such compounds as, at the very least, adjuncts for other appetite control and weight reduction techniques (such as proper diet and exercise regimens) is clearly evident in the increasing proportion of people, particularly Americans, who are clinically obese. Thus, the specific aims are to measure hypothesized decreases in intake of various foods following administration of antagonists specific for CB1 receptors. The proposed studies will use rats to examine the effects of a number of CB1 receptor antagonists and will also use a number of typical ingestive paradigms. These include intake of fat, carbohydrates and protein (macronutrients), food intake following insulin or 2-deoxy-D-glucose, and intake of palatable solutions (such as sucrose). The basic procedure involves establishing baseline levels of intake and then measuring how different doses of the drugs affect this intake. Drugs are delivered directly into the brain, bypassing metabolic constraints and allowing for measurement of effects of small (microgram) doses. Each rat receives all doses of a specific compound and serves as its own experimental control, thus creating a basic within-subjects design which reveals dose-dependent effects on behavior, in this case ingestion.